Bio-imaging technologies are essential for clinical as well as preclinical medical research and daily medical practice. For any imaging system, resolution and contrast are key performance factors. Resolution refers to the spatial detail that can be revealed, while contrast includes a wide range of parameters, from simple physical signal-to-noise ratio to functional and molecular selectivity and sensitivity.
Functional and molecular imaging is becoming increasingly important both for research and in the clinic. In this context, “functional” refers to detecting changes in metabolism and “molecular” refers to measurements of biological processes on the molecular or cellular level. It is generally desired to be able to perform such imaging in vivo.
Several techniques for imaging exist in the prior art, such as magnetic resonance imaging (MRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT), which provide different aspects of such imaging (from humans or human sized subjects to smaller subjects such as mice). However, the spatial resolution of these techniques is low, typically a few millimeters (PET and SPECT) or down to about one millimeter (MRI). Similar limitations apply for small-animal research tools such as luceferin-based bio-luminescence. Fundamental constraints in the techniques make it hard to envision large upcoming improvements.
Recently, x-ray imaging has received more attention for higher resolution imaging, primarily for providing morphological data, but also directed towards functional and molecular imaging.
One example of a system and method for x-ray fluorescence computed tomography imaging is disclosed in WO 2011/084625, in which there is described x-ray fluorescence computed tomography (XFCT) for molecular imaging of various cells loaded with metallic nanoparticles using polychromatic diagnostic energy x-rays. The XFCT is performed of a plurality of metallic nanoparticles within a cell. The nanoparticles are sized and configured to not only have an affinity for cell compounds, but also have a size small enough to be able to enter the cell or multicellular structures like tumors or tissue. A polychromatic x-ray source at diagnostic energy levels is energized to cause x-ray fluorescence of the nanoparticles.
However, this prior art XFCT system comes with some serious drawbacks related to noise and background radiation in the generated signal. Excitation of the nanoparticles themselves as well as Compton scattering produce a considerable background signal that must be filtered out or otherwise handled in order to be able to detect the desired fluorescence. Filters, spline-function data fitting, and piecewise cubic Hermitian polynomial interpolation is used in order to filter out the background and enable identification of the desired fluorescence. All in all, this limits the resolution and contrast of this prior-art system considerably.
Attempts have been made by Bernard L Jones et al. (Phys. Med. Biol. 57 (2012), N457-N467) to improve XFCT systems that use gold nanoparticles (GNPs) as fluorescence targets, wherein the polychromatic x-ray spectrum was filtered using lead (Pb) or preferably tin (Sn) filters to provide a filtered polychromatic excitation spectrum. Such filtering was said to facilitate detection of Kα fluorescence peaks from the GNPs by increasing the signal-to-background ratio. They noted that the ratio of gold fluorescence signal to delivered dose increased exponentially with tin filter thickness. However, the scan time to produce the same magnitude of gold fluorescence signal also increased with tin filter thickness at a much higher rate. It was thus concluded that it was imperative to use a higher power x-ray tube for the XFCT scanning in order to take advantage of an increased signal-to-dose ratio from the use of thicker filters.